MEIS1‑regulated miR‑488‑3p suppresses the malignant progression of laryngeal squamous cell carcinoma by targeting ACVR1C.

IF 5.8 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
International journal of molecular medicine Pub Date : 2025-09-01 Epub Date: 2025-07-19 DOI:10.3892/ijmm.2025.5583
Chunming Zhang, Wenjing Hao, Xinfang Wang, Huina Guo, Long He, Jiao Yang, Ying Wang, Xiwang Zheng, Zhongxun Li, Qi Han, Liqi Wen, Hongliang Liu
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引用次数: 0

Abstract

Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor originating from the mucosal epithelium of the larynx. MicroRNA (miR)‑488‑3p has non‑negligible multifaceted roles in some types of cancer; however, its association with LSCC has not yet been reported. Our prior RNA sequencing data indicated that miR‑488‑3p expression is downregulated in LSCC tissue, yet the detailed function and regulatory mechanism of miR‑488‑3p in LSCC remain unknown. In the present study, quantitative PCR analysis corroborated the significant downregulation of miR‑488‑3p in LSCC tumor tissues, with this downregulation being strongly associated with malignant progression in LSCC. Furthermore, overexpression of miR‑488‑3p suppressed LSCC cell proliferation, colony formation, migration, invasion, xenograft tumor growth and epithelial‑mesenchymal transition. Mechanistically, miR‑488‑3p directly interacted with the 3' untranslated region of activin A receptor type 1C (ACVR1C) and downregulated ACVR1C expression. Functional experiments revealed that miR‑488‑3p suppressed the malignant phenotypes of LSCC via ACVR1C. Additionally, bioinformatics analysis coupled with chromatin immunoprecipitation assay revealed that myeloid ecotropic viral integration site 1 (MEIS1) promoted the expression of miR‑488‑3p transcriptionally by directly binding its promoter region. Collectively, the results demonstrated that miR‑488‑3p acts as a tumor suppressor molecule in LSCC, and a role was established for the MEIS1/miR‑488‑3p/ACVR1C axis in regulating LSCC progression, thus providing novel potential biomarkers and targets for patients with LSCC.

MEIS1调控的miR - 488 - 3p通过靶向ACVR1C抑制喉鳞状细胞癌的恶性进展。
喉鳞癌(喉鳞癌)是一种常见的恶性肿瘤,起源于喉粘膜上皮。MicroRNA (miR)‑488‑3p在某些类型的癌症中具有不可忽视的多方面作用;然而,其与LSCC的关系尚未见报道。我们之前的RNA测序数据表明miR - 488 - 3p在LSCC组织中表达下调,但miR - 488 - 3p在LSCC中的详细功能和调节机制尚不清楚。在本研究中,定量PCR分析证实了miR - 488 - 3p在LSCC肿瘤组织中的显著下调,并且这种下调与LSCC的恶性进展密切相关。此外,miR - 488 - 3p过表达抑制LSCC细胞增殖、集落形成、迁移、侵袭、异种移植物肿瘤生长和上皮-间质转化。在机制上,miR - 488 - 3p直接与激活素A受体1C型(ACVR1C)的3'非翻译区相互作用,下调ACVR1C的表达。功能实验显示miR - 488 - 3p通过ACVR1C抑制LSCC的恶性表型。此外,生物信息学分析结合染色质免疫沉淀试验显示,髓系亲生态病毒整合位点1 (MEIS1)通过直接结合miR - 488 - 3p的启动子区,通过转录促进miR - 488 - 3p的表达。总之,结果表明miR - 488 - 3p在LSCC中作为肿瘤抑制分子,并且MEIS1/miR - 488 - 3p/ACVR1C轴在调节LSCC进展中的作用被确立,从而为LSCC患者提供了新的潜在生物标志物和靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
International journal of molecular medicine
International journal of molecular medicine 医学-医学:研究与实验
CiteScore
12.30
自引率
0.00%
发文量
124
审稿时长
3 months
期刊介绍: The main aim of Spandidos Publications is to facilitate scientific communication in a clear, concise and objective manner, while striving to provide prompt publication of original works of high quality. The journals largely concentrate on molecular and experimental medicine, oncology, clinical and experimental cancer treatment and biomedical research. All journals published by Spandidos Publications Ltd. maintain the highest standards of quality, and the members of their Editorial Boards are world-renowned scientists.
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